5KA0

Protein Tyrosine Phosphatase 1B Delta helix 7, open state

Summary for 5KA0

• Entry DOI: 10.2210/pdb5ka0/pdb
• Related: 5K9V 5K9W 5KA1 5KA2 5KA3 5KA4 5KA7 5KA8 5KA9 5KAA 5KAB 5KAC 5KAD
• Descriptor: Tyrosine-protein phosphatase non-receptor type 1, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, GLYCEROL, ... (5 entities in total)
• Functional Keywords: protein tyrosine phosphatase, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 34250.90

Authors

Choy, M.S.,Peti, W.,Page, R. (deposition date: 2016-06-01, release date: 2017-03-01, Last modification date: 2023-09-27)

Primary citation

Choy, M.S.,Li, Y.,Machado, L.E.,Kunze, M.B.,Connors, C.R.,Wei, X.,Lindorff-Larsen, K.,Page, R.,Peti, W.
Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery.
Mol. Cell, 65:644-658.e5, 2017

PubMed Abstract: Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug target for diabetes and cancer that catalyzes the dephosphorylation of numerous substrates in essential signaling pathways. By combining new experimental and computational data on WT-PTP1B and ≥10 PTP1B variants in multiple states, we discovered a fundamental and evolutionarily conserved CH/π switch that is critical for positioning the catalytically important WPD loop. Furthermore, our data show that PTP1B uses conformational and dynamic allostery to regulate its activity. This shows that both conformational rigidity and dynamics are essential for controlling protein activity. This connection between rigidity and dynamics at different timescales is likely a hallmark of all enzyme function.

PubMed: 28212750
DOI: 10.1016/j.molcel.2017.01.014

Experimental method

X-RAY DIFFRACTION (1.991 Å)